Liquid chromatograph-mass spectrometer combination
By setting up low-pressure and high-pressure liquid chromatography channels in the liquid chromatography-mass spectrometry (LC-MS) equipment, the high cost problem caused by high pressure in the existing technology is solved, achieving efficient sample detection and cost reduction.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SHENZHEN MINDRAY BIO MEDICAL ELECTRONICS CO LTD
- Filing Date
- 2025-12-25
- Publication Date
- 2026-06-26
AI Technical Summary
The production and maintenance costs of existing ultra-high performance liquid chromatography-tandem mass spectrometry equipment are high, mainly due to the increased manufacturing difficulty and maintenance costs caused by high pressure.
A liquid chromatography-mass spectrometry (LC-MS) system is used, with low-pressure and high-pressure liquid chromatography channels. The low-pressure liquid chromatography channel operates at a pressure less than or equal to 20 MPa, while the high-pressure liquid chromatography channel operates at a pressure greater than 20 MPa. These channels are connected in parallel to the same mass spectrometry detection device to achieve low-pressure and high-pressure liquid chromatography elution functions.
It reduces the manufacturing difficulty and maintenance cost of liquid chromatography-mass spectrometry (LC-MS) equipment, improves sample detection efficiency, and meets the detection needs of different samples.
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Figure CN122282976A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of medical devices, and more particularly to a liquid chromatography-mass spectrometry (LC-MS) device. Background Technology
[0002] In related technologies, clinical mass spectrometry detection of trace substances (concentrations as low as pg / mL) such as vitamin D, steroid hormones, and catecholamines employs ultra-high performance liquid chromatography-mass spectrometry (UPLC / UHPLC) tandem mass spectrometry, equipped with chromatographic columns of long length, small inner diameter, and small particle size (e.g., 2.1 mm * 100 mm, 1.7 μm) to meet clinical testing needs. However, the pressure of UPLC / UHPLC systems has also increased significantly, with column pressures generally exceeding 40 MPa, and some even reaching baseline pressures above 60 MPa and peak pressures exceeding 80 MPa. This leads to a substantial increase in the manufacturing difficulty, production cost, and maintenance cost of high-pressure pumps, high-pressure valves, and high-pressure pipelines, and also increases the frequency of failures. Summary of the Invention
[0003] The first objective of this invention is to provide a liquid chromatography-mass spectrometry (LC-MS) device that aims to solve the technical problem of high production and maintenance costs in ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS / MS) devices in related technologies.
[0004] To achieve the above objectives, the present invention provides a liquid chromatography-mass spectrometry (LC-MS) device, comprising: A sample storage device, the sample storage device being used to place a first sample container loaded with a first sample to realize the loading of the first sample, and to place a second sample container loaded with a second sample to realize the loading of the second sample, the first sample including a target analyte; A pretreatment device for pretreating a first sample from a first sample container of the sample storage device to obtain a first test solution, and for pretreating a second sample from a second sample container of the sample storage device to obtain a second test solution. A chromatographic device, comprising a reagent transfer assembly, at least one first liquid chromatography channel, and at least one second liquid chromatography channel, wherein the reagent transfer assembly is used to transfer at least a portion of the first reagent obtained by pretreatment by the pretreatment device to the first liquid chromatography channel and to transfer at least a portion of the second reagent obtained by pretreatment by the pretreatment device to the second liquid chromatography channel, wherein the first liquid chromatography channel is used to drive a liquid fluid at a first working pressure to elute the first reagent to form a first analyte, and the second liquid chromatography channel is used to drive a liquid fluid at a second working pressure to elute the second reagent to form a second analyte; A mass spectrometry detection device, wherein at least one first liquid chromatography channel and at least one second liquid chromatography channel are respectively connected to the same mass spectrometry detection device, the mass spectrometry detection device is used to perform mass spectrometry detection on the first test liquid flowing out of the first liquid chromatography channel and obtain first mass spectrometry detection information, and is used to perform mass spectrometry detection on the second test liquid flowing out of the second liquid chromatography channel and obtain second mass spectrometry detection information. A controller configured to process the first mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the first sample; The controller is also configured to process the second mass spectrometry detection information and output the mass spectrometry detection result of the second sample; The first sample and the second sample are two different samples; The first sample container and the second sample container are two independent sample containers; The first working pressure is less than or equal to 20 MPa, and the second working pressure is greater than 20 MPa.
[0005] In one implementation, the second working pressure is greater than or equal to 40 MPa.
[0006] In one implementation, the second working pressure is greater than or equal to 60 MPa.
[0007] In one implementation, the second working pressure is greater than or equal to 80 MPa.
[0008] In one implementation, the first working pressure is greater than or equal to 2 MPa and less than or equal to 15 MPa. In one embodiment, the first liquid chromatography channel includes a first reagent preparation channel, at least one first drive pump, and at least one first chromatographic column. The reagent transfer assembly, the first drive pump, and the first chromatographic column are respectively connected to the first reagent preparation channel. The reagent transfer assembly is used to transfer at least a portion of the first reagent obtained by the pretreatment device to the first reagent preparation channel. The at least one first drive pump is used to drive the first reagent in the first reagent preparation channel through the chromatographic column to adsorb the first reagent onto the chromatographic column, and to drive the liquid fluid through the chromatographic column to elute the first reagent adsorbed on the chromatographic column to form the first test solution. The second liquid chromatography channel includes a second reagent preparation channel, at least one second drive pump, and at least one second chromatographic column. The reagent transfer assembly, the second drive pump, and the second chromatographic column are respectively connected to the second reagent preparation channel. The reagent transfer assembly is used to transfer at least a portion of the second reagent obtained by the pretreatment device to the second reagent preparation channel. The at least one second drive pump is used to drive the second reagent in the second reagent preparation channel through the chromatographic column to adsorb the second reagent onto the chromatographic column, and to drive the liquid fluid through the chromatographic column to elute the second reagent adsorbed on the chromatographic column to form the second test solution. The rated working pressure of the first drive pump is less than or equal to 20 MPa, and the rated working pressure of the second drive pump is greater than 20 MPa. The dimensional parameters of the first chromatographic column are different from those of the second chromatographic column; The first test solution preparation channel and the second test solution preparation channel may be the same test solution preparation channel or different test solution preparation channels.
[0009] In one embodiment, the first chromatographic column includes a first column having a first inner cavity and a first packing material filled in the first inner cavity; The second chromatographic column includes a second column having a second inner cavity and a second packing material filled within the second inner cavity; The dimensional parameters of the first chromatographic column are different from those of the second chromatographic column, including at least one of the following situations: the length of the first chromatographic column is less than the length of the second chromatographic column, and the inner diameter of the first inner cavity is greater than the inner diameter of the second inner cavity.
[0010] In one embodiment, the length of the first chromatographic column is greater than or equal to 5 mm and less than or equal to 30 mm, and the length of the second chromatographic column is greater than or equal to 50 mm and less than or equal to 150 mm. And / or, the inner diameter of the first inner cavity is greater than 2.1 mm and less than or equal to 4.0 mm, and the inner diameter of the second inner cavity is greater than or equal to 1.0 mm and less than or equal to 2.1 mm.
[0011] In one embodiment, the volume of the first inner cavity is greater than or equal to 0.063 mL and less than or equal to 0.38 mL.
[0012] In one embodiment, the second drive pump is also configured to switchly connect to at least one of the first chromatographic columns; The second drive pump has a first working mode and a second working mode. In the first working mode, the second drive pump is used to communicate with the second chromatographic column and drive the liquid phase fluid at the second working pressure to elute the second test solution adsorbed on the second chromatographic column to form the second test solution. In the second working mode, the second drive pump is used to communicate with the first chromatographic column and drive the liquid phase fluid at the first working pressure to elute the first test solution adsorbed on the first chromatographic column to form the first test solution.
[0013] In one embodiment, the number of the first chromatographic columns is multiple, and the liquid chromatography-mass spectrometry (LC-MS) device further includes a first switching device and a second switching device. The multiple first chromatographic columns are connected in parallel between the first switching device and the second switching device. The first drive pump can switch to connect to the multiple first chromatographic columns through the first switching device, and the mass spectrometry detection device can switch to connect to the multiple first chromatographic columns through the second switching device. And / or, the number of the second chromatographic columns is multiple, and the liquid chromatography-mass spectrometry device further includes a third switching device and a fourth switching device. The multiple second chromatographic columns are connected in parallel between the third switching device and the fourth switching device. The second drive pump can switch to connect to the multiple second chromatographic columns through the third switching device, and the mass spectrometry detection device can switch to connect to the multiple second chromatographic columns through the fourth switching device.
[0014] In one implementation, the target analyte includes at least one of vitamin D, steroid hormones, and catecholamines; And / or, the output of the mass spectrometry detection results of the first sample includes: outputting the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the first sample.
[0015] In one implementation, both the first sample and the second sample are samples collected from human or animal bodies. And / or, both the first sample and the second sample are blood samples.
[0016] In one embodiment, the controller is further configured to: control the first liquid chromatography channel to prepare at least two liquids into liquid phase fluids of different concentrations according to a first preset concentration control method, and drive the liquid phase fluids of different concentrations to perform gradient elution on the first test solution at the first working pressure, thereby forming the first test solution; And / or, the controller is further configured to: control the second liquid chromatography channel to prepare at least two liquids into liquid phase fluids of different concentrations according to a second preset concentration control method, and drive the liquid phase fluids of different concentrations to perform gradient elution on the second test solution with the second working pressure, thereby forming the second test solution.
[0017] In one implementation, the pretreatment device uses at least one of magnetic separation, solid-phase extraction, liquid-liquid extraction, and protein precipitation to pretreatment the first sample and the second sample, respectively. In one embodiment, the liquid chromatography-mass spectrometry (LC-MS) device further includes an information acquisition device, which is used to acquire at least one of the following information: information about the sample container, and information about the sample loaded in the sample container; wherein the information about the sample includes at least the type information of the sample and / or the analyte information of the sample; Before processing the first mass spectrometry detection information or the second mass spectrometry detection information, the controller is further configured to: Based on the information obtained from the device feedback, determine the type of the sample container from the sample storage device, or determine the type of sample loaded in the sample container from the sample storage device, or determine the test item information of the sample in the sample container from the sample storage device. When the information obtained from the information acquisition device feedback determines that the sample container from the sample storage device is of the first sample container type, or determines that the sample from the sample container from the sample storage device is of the first sample type, or determines that the test item of the sample from the sample container from the sample storage device contains the first target item, the pretreatment device is controlled to pretreatment the sample in the sample container to obtain the first test solution, the test solution transfer component is controlled to transfer at least a portion of the first test solution obtained by the pretreatment device to the first liquid chromatography channel, the first liquid chromatography channel is controlled to drive the liquid phase fluid at the first working pressure to elute the first test solution to form the first test solution, and the mass spectrometry detection device is controlled to perform mass spectrometry detection on the first test solution flowing out of the first liquid chromatography channel and obtain the first mass spectrometry detection information. When the information obtained from the information acquisition device feedback determines that the sample container from the sample storage device is the second sample container, or determines that the sample in the sample container from the sample storage device is the second sample, or determines that the test item of the sample in the sample container from the sample storage device contains the second target item, the pretreatment device is controlled to pretreatment the sample in the sample container to obtain the second test solution, the test solution transfer component is controlled to transfer at least a portion of the second test solution obtained by the pretreatment device to the second liquid chromatography channel, the second liquid chromatography channel is controlled to drive the liquid phase fluid to elute the second test solution at the second working pressure to form the second test solution, and the mass spectrometry detection device is controlled to perform mass spectrometry detection on the second test solution flowing out of the second liquid chromatography channel and obtain the second mass spectrometry detection information; Alternatively, the sample storage device may have a first loading area and a second loading area independent of the first loading area. The first loading area is used to place the first sample container containing the first sample to load the first sample, and the second loading area is used to place the second sample container containing the second sample to load the second sample. Before processing the first mass spectrometry detection information, the controller is further configured to: acquire information that a sample container is placed in the first loading area; control the pretreatment device to pretreat the sample in the sample container to obtain the first test solution; control the test solution transfer component to transfer at least a portion of the first test solution obtained by the pretreatment device to the first liquid chromatography channel; control the first liquid chromatography channel to drive the liquid phase fluid at the first working pressure to elute the first test solution to form the first test solution; and control the mass spectrometry detection device to perform mass spectrometry detection on the first test solution flowing out of the first liquid chromatography channel and obtain the first mass spectrometry detection information. Before processing the second mass spectrometry detection information, the controller is further configured to: acquire information that a sample container is placed in the second loading area; control the pretreatment device to pretreat the sample in the sample container to obtain the second test solution; control the test solution transfer component to transfer at least a portion of the second test solution obtained by the pretreatment device to the second liquid chromatography channel; control the second liquid chromatography channel to drive the liquid phase fluid at the second working pressure to elute the second test solution to form the second test solution; and control the mass spectrometry detection device to perform mass spectrometry detection on the second test solution flowing out of the second liquid chromatography channel and obtain the second mass spectrometry detection information.
[0018] A second objective of this invention is to provide a liquid chromatography-mass spectrometry (LC-MS) device, which includes: A sample storage device, the sample storage device being used to place a first sample container loaded with a first sample to realize the loading of the first sample, and to place a second sample container loaded with a second sample to realize the loading of the second sample, the first sample including a target analyte; A pretreatment device for pretreating a first sample from a first sample container of the sample storage device to obtain a first test solution, and for pretreating a second sample from a second sample container of the sample storage device to obtain a second test solution. A chromatographic device, comprising a reagent transfer assembly, at least one first liquid chromatography channel, and at least one second liquid chromatography channel, wherein the reagent transfer assembly is used to transfer at least a portion of the first reagent obtained by pretreatment by the pretreatment device to the first liquid chromatography channel and to transfer at least a portion of the second reagent obtained by pretreatment by the pretreatment device to the second liquid chromatography channel, wherein the first liquid chromatography channel is used to drive a liquid fluid to elute the first reagent to form a first analyte, and the second liquid chromatography channel is used to drive a liquid fluid to elute the second reagent to form a second analyte; A mass spectrometry detection device, wherein at least one first liquid chromatography channel and at least one second liquid chromatography channel are respectively connected to the same mass spectrometry detection device, the mass spectrometry detection device is used to perform mass spectrometry detection on the first test liquid flowing out of the first liquid chromatography channel and obtain first mass spectrometry detection information, and is used to perform mass spectrometry detection on the second test liquid flowing out of the second liquid chromatography channel and obtain second mass spectrometry detection information. A controller configured to process the first mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the first sample; The controller is also configured to process the second mass spectrometry detection information and output the mass spectrometry detection result of the second sample; The first sample and the second sample are two different samples; The first sample container and the second sample container are two independent sample containers; The first liquid chromatography channel includes at least one first chromatographic column, and the second liquid chromatography channel includes at least one second chromatographic column, wherein the size parameters of the first chromatographic column are different from the size parameters of the second chromatographic column.
[0019] In one embodiment, the first chromatographic column includes a first column having a first inner cavity and a first packing material filled in the first inner cavity; The second chromatographic column includes a second column having a second inner cavity and a second packing material filled within the second inner cavity; The dimensional parameters of the first chromatographic column are different from those of the second chromatographic column, including at least one of the following situations: the length of the first chromatographic column is less than the length of the second chromatographic column, and the inner diameter of the first inner cavity is greater than the inner diameter of the second inner cavity.
[0020] In one embodiment, the length of the first chromatographic column is greater than or equal to 5 mm and less than or equal to 30 mm, and the length of the second chromatographic column is greater than or equal to 50 mm and less than or equal to 150 mm. And / or, the inner diameter of the first inner cavity is greater than 2.1 mm and less than or equal to 4.0 mm, and the inner diameter of the second inner cavity is greater than or equal to 1.0 mm and less than or equal to 2.1 mm.
[0021] A third objective of this invention is to provide a liquid chromatography-mass spectrometry (LC-MS) device, which includes: A sample storage device, the sample storage device being used to place a first sample container loaded with a first sample to realize the loading of the first sample, and to place a second sample container loaded with a second sample to realize the loading of the second sample, the first sample including a target analyte; A pretreatment device for pretreating a first sample from a first sample container of the sample storage device to obtain a first test solution, and for pretreating a second sample from a second sample container of the sample storage device to obtain a second test solution. A chromatographic device, comprising a reagent transfer assembly, at least one first liquid chromatography channel, and at least one second liquid chromatography channel, wherein the reagent transfer assembly is used to transfer at least a portion of the first reagent obtained by pretreatment by the pretreatment device to the first liquid chromatography channel and to transfer at least a portion of the second reagent obtained by pretreatment by the pretreatment device to the second liquid chromatography channel, wherein the first liquid chromatography channel is used to drive a liquid fluid to elute the first reagent to form a first analyte, and the second liquid chromatography channel is used to drive a liquid fluid to elute the second reagent to form a second analyte; A mass spectrometry detection device, wherein at least one first liquid chromatography channel and at least one second liquid chromatography channel are respectively connected to the same mass spectrometry detection device, the mass spectrometry detection device is used to perform mass spectrometry detection on the first test liquid flowing out of the first liquid chromatography channel and obtain first mass spectrometry detection information, and is used to perform mass spectrometry detection on the second test liquid flowing out of the second liquid chromatography channel and obtain second mass spectrometry detection information. A controller configured to process the first mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the first sample; The controller is also configured to process the second mass spectrometry detection information and output the mass spectrometry detection result of the second sample; The first sample and the second sample are two different samples; The first sample container and the second sample container are two independent sample containers; The first liquid chromatography channel includes at least one first drive pump, and the second liquid chromatography channel includes at least one second drive pump. The rated operating pressure of the first drive pump is less than or equal to 20 MPa, and the rated operating pressure of the second drive pump is greater than 20 MPa.
[0022] In one embodiment, the rated operating pressure of the first drive pump is greater than or equal to 2 MPa and less than or equal to 15 MPa, and the rated operating pressure of the second drive pump is greater than or equal to 40 MPa. Alternatively, the rated operating pressure of the first drive pump is greater than or equal to 2 MPa and less than or equal to 15 MPa, or the rated operating pressure of the first drive pump is greater than or equal to 60 MPa. Alternatively, the rated operating pressure of the first drive pump is greater than or equal to 2 MPa and less than or equal to 15 MPa, or the rated operating pressure of the first drive pump is greater than or equal to 80 MPa.
[0023] The liquid chromatography-mass spectrometry (LC-MS) device provided by this invention, by setting at least one first liquid chromatography channel and at least one second liquid chromatography channel in the chromatographic device, setting the first working pressure of the first liquid chromatography channel to less than or equal to 20 MPa, and setting the second working pressure of the second liquid chromatography channel to greater than 20 MPa, and connecting each first liquid chromatography channel and each second liquid chromatography channel to the same mass spectrometry detection device, allows the LC-MS device to simultaneously possess low-pressure liquid chromatography and high-pressure liquid chromatography elution functions. This is beneficial for meeting the detection needs of different samples and avoids the problem of high production and maintenance costs associated with using only high-pressure liquid chromatography channels greater than 20 MPa for LC-MS devices. Furthermore, multiple liquid chromatography channels can operate in parallel, which helps improve sample detection efficiency. Attached Figure Description
[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.
[0025] Figure 1 This is a schematic diagram of the structure of the liquid chromatography-mass spectrometry device provided in the embodiments of the present invention; Figure 2 This is a schematic diagram of the liquid path of a single first chromatographic column provided in an embodiment of the present invention; Figure 3 This is a schematic diagram of the dimensions of the first chromatographic column provided in an embodiment of the present invention; Figure 4 This is a comparative schematic diagram of rapid gradient separation and elution using chromatographic columns of different lengths provided in the embodiments of the present invention; Figure 5 This is a comparative schematic diagram of rapid gradient separation and elution using chromatographic columns with different inner diameters, provided in an embodiment of the present invention. Figure 6 This is a comparative schematic diagram of rapid gradient separation and elution using chromatographic columns of different particle sizes provided in the embodiments of the present invention; Figure 7 This is a schematic diagram comparing the detection results of steroid hormones obtained by using the scheme of the present invention and related technical solutions respectively; Figure 8 This is a schematic diagram comparing the detection results of vitamin D obtained by using the scheme of the present invention and related technical solutions. Figure 9 This is a schematic diagram of the principle of the liquid chromatography-mass spectrometry device provided in the embodiments of the present invention.
[0026] Explanation of reference numerals in the attached figures: 10, Liquid Chromatography-Mass Spectrometry (LC-MS) equipment; 100, Chromatographic device; 101, First LC channel; 110, First chromatographic column; 111, First inner cavity; 120, Liquid fluid delivery assembly; 121, First drive pump; 123, First confluence component; 130, First reagent preparation channel; 140, Reagent transfer assembly; 102, Second LC channel; 200, Mass spectrometry detection device; 300, Pretreatment device; 310, Magnetic separation component; 320, Magnetic bead elution component; 330, Reagent storage component; 340, Reagent dispensing component; 350, Pipette component; 360, Reaction vessel supply component; 400, Sample storage device; 20, First container; 30, Second container; L, Length of the first chromatographic column; d, Inner diameter. Detailed Implementation
[0027] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.
[0028] like Figures 1 to 9As shown, a liquid chromatography-mass spectrometry (LC-MS) device 10 provided in the first aspect of this invention includes a sample storage device 400, a pretreatment device 300, a chromatographic device 100, a mass spectrometry detection device 200, and a controller. The sample storage device 400 is used to hold a first sample container containing a first sample for loading the first sample, and to hold a second sample container containing a second sample for loading the second sample. The pretreatment device 300 is used to pretreatment the first sample from the first sample container of the sample storage device 400 to obtain a first test solution, and to pretreatment the second sample from the second sample container of the sample storage device 400 to obtain a second test solution. The chromatographic device 100 includes a reagent transfer assembly 140, at least one first liquid chromatography channel 101, and at least one second liquid chromatography channel 102. The reagent transfer assembly 140 is used to transfer at least a portion of the first reagent obtained by pretreatment by the pretreatment device 300 to the first liquid chromatography channel 101 and to transfer at least a portion of the second reagent obtained by pretreatment by the pretreatment device 300 to the second liquid chromatography channel 102. The first liquid chromatography channel 101 is used to drive a liquid fluid at a first working pressure to elute the first reagent to form a first analyte. The second liquid chromatography channel 102 is used to drive a liquid fluid at a second working pressure to elute the second reagent to form a second analyte. At least one first liquid chromatography channel 101 and at least one second liquid chromatography channel 102 are respectively connected to the same mass spectrometry detection device 200. The mass spectrometry detection device 200 is used to perform mass spectrometry detection on a first analyte flowing out of the first liquid chromatography channel 101 and obtain first mass spectrometry detection information, and to perform mass spectrometry detection on a second analyte flowing out of the second liquid chromatography channel 102 and obtain second mass spectrometry detection information. The controller is configured to process the first mass spectrometry detection information and output the mass spectrometry detection result of the first sample. The controller is also configured to process the second mass spectrometry detection information and output the mass spectrometry detection result of the second sample. The first sample and the second sample are two different samples; the first sample container and the second sample container are two independent sample containers; the first working pressure is less than or equal to 20 MPa, and the second working pressure is greater than 20 MPa. In this embodiment, the liquid chromatography-mass spectrometry (LC-MS) device 10 simultaneously possesses both low-pressure liquid chromatography (LPLC) and high-pressure liquid chromatography (HPLC) elution functions (the low-pressure and HPLC functions refer to the first LC channel 101 and the second LC channel 102 in comparison). This facilitates meeting the detection needs of different samples and avoids the problem of high production and maintenance costs associated with using only HPLC channels greater than 20 MPa for all samples. Furthermore, multiple LC channels can operate in parallel, which improves sample detection efficiency.
[0029] In one implementation, the second working pressure is greater than or equal to 40 MPa. The second liquid chromatography channel 102 is an ultra-high pressure liquid chromatography channel, which has high resolution and detection sensitivity, and can be used for the separation of trace complex mixtures and high-precision research.
[0030] As one implementation method, the second working pressure is greater than or equal to 60 MPa.
[0031] As one implementation method, the second working pressure is greater than or equal to 80 MPa.
[0032] In one implementation, the first working pressure is greater than or equal to 2 MPa and less than or equal to 15 MPa. The working pressure of the first liquid chromatography channel 101 is roughly equivalent to that of a conventional liquid chromatography channel. Connecting it in parallel with the second liquid chromatography channel 102 in the same liquid chromatography-mass spectrometry device 10 is beneficial for meeting the detection needs of different types of samples. In one implementation, both the first and second samples are samples collected from human or animal bodies.
[0033] In one implementation method, both the first and second samples are blood samples.
[0034] In one implementation, the first sample includes a target analyte. The aforementioned output of the mass spectrometry detection result of the first sample includes: outputting the mass spectrometry detection result of the target analyte in the first sample.
[0035] As one implementation method, the target analyte includes at least one of vitamin D, steroid hormones, and catecholamines.
[0036] As one implementation, outputting the mass spectrometry detection results of the first sample includes: outputting the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the first sample.
[0037] As one implementation method, the mass spectrometry detection results of the first sample are output, including: outputting the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the first sample. That is, the embodiments of the present invention use an operating pressure of less than 20 MPa, which can meet the detection requirements of trace substances such as vitamin D, steroid hormones, and catecholamines. This allows the liquid chromatography-mass spectrometry (LC-MS) device 10 to achieve detection performance similar to or even exceeding that of ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) devices under low-pressure conditions, thereby greatly reducing the manufacturing difficulty, production cost, maintenance cost, and failure frequency of the LC-MS device 10.
[0038] This invention combines low-pressure and high-pressure liquid chromatography channels (first liquid chromatography channel 101 and second liquid chromatography channel 102) to achieve efficient combined application of various clinical mass spectrometry detection items with different liquid chromatography separation requirements, such as vitamin D, steroid hormones, catecholamines and drug concentration detection, thereby optimizing the cost of the liquid chromatography-mass spectrometry coupling device 10, the cost of liquid consumables and the detection efficiency.
[0039] In one embodiment, the first liquid chromatography channel 101 includes a first reagent preparation channel 130, at least one first drive pump 121, and at least one first chromatographic column 110. A reagent transfer assembly 140, the first drive pump 121, and the first chromatographic column 110 are respectively connected to the first reagent preparation channel 130. The reagent transfer assembly 140 is used to transfer at least a portion of the first reagent obtained by pretreatment by the pretreatment device 300 to the first reagent preparation channel 130. The at least one first drive pump 121 is used to drive the first reagent in the first reagent preparation channel 130 through the chromatographic column via liquid phase fluid to adsorb the first reagent onto the chromatographic column, and to drive liquid phase fluid through the chromatographic column to elute the first reagent adsorbed on the chromatographic column to form a first analyte. The rated operating pressure of the first drive pump 121 is less than or equal to 20 MPa.
[0040] In one embodiment, the rated operating pressure of the first drive pump 121 is greater than or equal to 2 MPa and less than or equal to 15 MPa.
[0041] In one embodiment, each first liquid chromatography channel 101 includes two first drive pumps 121, one of which is used to draw a first liquid from the first container 20 and deliver the drawn first liquid toward the chromatography column, and the other is used to draw a second liquid from the second container 30 and deliver the drawn second liquid toward the chromatography column.
[0042] In one implementation, the ionic strength of the first liquid is less than that of the second liquid. Specifically, the first liquid may be liquid A, and the second liquid may be liquid B.
[0043] In one embodiment, the first liquid contains a first buffer salt, and the second liquid contains a second buffer salt; the concentration of the first liquid is the concentration of the first buffer salt in the first liquid, and the concentration of the second liquid is the concentration of the second buffer salt in the second liquid. The first buffer salt and the second buffer salt can be the same buffer salt or two different buffer salts; that is, the buffer salt in the first liquid and the buffer salt in the second liquid can be the same buffer salt or different buffer salts. When the buffer salt in the first liquid and the buffer salt in the second liquid are the same buffer salt, the concentration of the liquid phase fluid formed by the first liquid and the second liquid is the concentration of that buffer salt in the liquid phase fluid; when the buffer salt in the first liquid and the buffer salt in the second liquid are different buffer salts, the concentration of the liquid phase fluid formed by the first liquid and the second liquid is the sum of the concentrations of the first buffer salt and the second buffer salt in the liquid phase fluid.
[0044] In one embodiment, the second liquid chromatography channel 102 includes a second reagent preparation channel, at least one second drive pump, and at least one second chromatographic column. The reagent transfer assembly 140, the second drive pump, and the second chromatographic column are respectively connected to the second reagent preparation channel. The reagent transfer assembly 140 is used to transfer at least a portion of the second reagent obtained by the pretreatment device 300 to the second reagent preparation channel. The at least one second drive pump is used to drive the second reagent in the second reagent preparation channel through the chromatographic column via liquid phase fluid to adsorb the second reagent onto the chromatographic column, and to drive liquid phase fluid through the chromatographic column to elute the adsorbed second reagent onto the chromatographic column to form a second analyte. The rated operating pressure of the second drive pump is greater than 20 MPa. The first reagent preparation channel 130 and the second reagent preparation channel may be the same reagent preparation channel or different reagent preparation channels.
[0045] In one implementation, the rated operating pressure of the second drive pump is greater than or equal to 40 MPa.
[0046] In one implementation, the rated operating pressure of the second drive pump is greater than or equal to 60 MPa.
[0047] In one implementation, the dimensional parameters of the first chromatographic column 110 are different from those of the second chromatographic column.
[0048] In one embodiment, the first chromatographic column 110 includes a first column having a first inner cavity 111 and a first packing material filled within the first inner cavity 111. The second chromatographic column includes a second column having a second inner cavity and a second packing material filled within the second inner cavity. The dimensional parameters of the first chromatographic column 110 differ from those of the second chromatographic column, including at least one of the following situations: the length L of the first chromatographic column is less than the length of the second chromatographic column, and the inner diameter dd of the first inner cavity 111 is greater than the inner diameter dd of the second inner cavity.
[0049] In one implementation, the length L of the first chromatographic column is greater than 0 mm and less than 50 mm. The first chromatographic column 110 has a first end and a second end spaced apart and opposite to each other. The first end forms a first inlet, and the second end forms a first outlet. The test solution and liquid phase fluid can flow into the chromatographic column from the first inlet, and the analyte or waste liquid formed by elution can flow out of the chromatographic column from the first outlet. The distance between the first end and the second end is the length L of the first chromatographic column. In the related technologies prior to this application, liquid chromatography-tandem mass spectrometry equipment used for detecting trace substances such as vitamin D, steroid hormones, and catecholamines requires a relatively long chromatographic column (e.g., a column with a length greater than 50 mm and less than or equal to 150 mm) to increase the theoretical plate number. This theoretical plate number is suitable for long-term separation requirements of partial isocratic elution, such as the detection and analysis of more complex scientific research samples; or, given a longer chromatographic column, the sample detection and analysis time can be appropriately shortened by increasing the flow rate, but this will result in ultra-high system pressure. In response to the need for rapid and efficient clinical testing, this invention adopts a rapid gradient separation and elution method. Within a certain range, using a shorter first chromatographic column 110 (less than 50 mm) provides better clinical testing performance: analysis can be completed quickly by maintaining a low flow rate (0.3-0.6 mL / min), the separated analyte peaks are more favorable, and the shorter first chromatographic column 110 can result in lower system pressure, which is a significant advantage.
[0050] In one implementation method, the length L of the first chromatographic column is greater than or equal to 3 mm and less than or equal to 35 mm. Using a first chromatographic column 110 within this length range, the detection requirements for trace substances such as vitamin D, steroid hormones, and catecholamines can be met under low-pressure conditions.
[0051] In one implementation, the length L of the first chromatographic column is greater than or equal to 5 mm and less than or equal to 30 mm, and the length of the second chromatographic column is greater than or equal to 50 mm and less than or equal to 150 mm. This implementation, by selecting a suitable effective length for the first chromatographic column 110, can reduce the diffusion of excess column volume and the non-specific adsorption loss of excess packing material, while significantly reducing column pressure. This facilitates maintaining or even further improving the performance of liquid chromatography-tandem mass spectrometry detection of trace substances such as vitamin D, steroid hormones, and catecholamines under low-pressure conditions.
[0052] In one implementation, the inner diameter dd of the first inner cavity 111 is greater than 2.1 mm and less than 4.6 mm. In prior art, liquid chromatography-tandem mass spectrometry (LC-MS / MS) for detecting trace amounts of substances such as vitamin D, steroid hormones, and catecholamines required columns with a smaller inner diameter dd (e.g., columns with an inner diameter dd greater than or equal to 1.0 mm and less than or equal to 2.1 mm) to reduce lateral diffusion during separation, decrease column bed volume (i.e., inner cavity volume), and shorten latency (dead time). However, a very small inner diameter dd leads to a significant increase in column pressure, increasing system pressure, and also increases the length of the target analyte bonded to the packing material, resulting in a broader peak and affecting resolution. In this embodiment, the first column 110 with an inner diameter dd (greater than 2.1 mm and less than 4.6 mm) differs from both ultra-high efficiency HPLC (1.0 mm~2.1 mm) and conventional HPLC (4.6 mm~10 mm) in related technologies, thus achieving both low pressure and high resolution.
[0053] In one implementation, the inner diameter dd of the first inner cavity 111 is greater than 2.1 mm and less than or equal to 4.0 mm, and the inner diameter dd of the second inner cavity is greater than or equal to 1.0 mm and less than or equal to 2.1 mm. In this implementation, by selecting a suitable inner diameter dd of the first chromatographic column 110, the length of the binding region between the target analyte and the packing material is narrowed, which helps to reduce peak width and improve resolution. Simultaneously, it can significantly reduce column pressure, thereby improving the performance of liquid chromatography-tandem mass spectrometry detection of trace substances such as vitamin D, steroid hormones, and catecholamines under low-pressure conditions.
[0054] In one embodiment, the length L of the first chromatographic column is greater than or equal to 5 mm and less than or equal to 30 mm, and the inner diameter dd of the first inner cavity 111 is greater than 2.1 mm and less than or equal to 4.0 mm.
[0055] In one implementation, the volume of the first inner cavity 111 is greater than or equal to 0.063 mL and less than or equal to 0.38 mL. If the column bed volume (i.e., the inner cavity volume) is too large, it will lead to excessive retention of the target analyte by the chromatographic column, which is not conducive to the rapid elution and separation of the target analyte, and will also increase the loss due to non-specific adsorption of the target analyte, resulting in a decrease in recovery rate and sensitivity. If the column bed volume is too small, it will lead to insufficient retention of the target analyte by the chromatographic column or supersaturation, resulting in sample loss and affecting the retention separation effect and sensitivity. In this implementation, the volume of the first inner cavity 111 is set to be greater than or equal to 0.063 mL and less than or equal to 0.38 mL, so that the first chromatographic column 110 can meet the rapid separation requirements for clinical detection of trace substances such as vitamin D, steroid hormones, and catecholamines.
[0056] In one embodiment, the second drive pump is also configured to switchably connect to at least one first chromatographic column 110. The second drive pump has a first operating mode and a second operating mode. In the first operating mode, the second drive pump is connected to the second chromatographic column and drives a liquid phase fluid at a second operating pressure to elute a second sample solution adsorbed on the second chromatographic column to form a second analyte. In the second operating mode, the second drive pump is also connected to the first chromatographic column 110 and drives a liquid phase fluid at a first operating pressure to elute a first sample solution adsorbed on the first chromatographic column 110 to form a first analyte. The second drive pump can be reused to provide driving force for a low-pressure liquid chromatography channel.
[0057] In one implementation, there are multiple first chromatographic columns 110. The liquid chromatography-mass spectrometry (LC-MS) device 10 also includes a first switching device and a second switching device. Multiple first chromatographic columns 110 are connected in parallel between the first switching device and the second switching device. A first drive pump 121 can be switched to connect to multiple first chromatographic columns 110 via the first switching device, and a mass spectrometry detection device 200 can be switched to connect to multiple first chromatographic columns 110 via the second switching device. In this implementation, by setting multiple first chromatographic columns 110 in parallel, multiple samples can be detected in parallel, thereby improving the detection efficiency of batch samples. Each first chromatographic column 110 requires two first drive pumps 121. If all drive pumps are ultra-high pressure pumps (operating pressure of 40 MPa), the cost of the LC-MS device 10 will be very high. Therefore, this implementation uses a first drive pump 121 with a rated operating pressure of less than or equal to 20 MPa, which can greatly reduce the cost of the LC-MS device 10. Of course, in specific applications, as an alternative implementation, the number of first chromatographic columns 110 can also be only one.
[0058] In one implementation, there are multiple second chromatographic columns. The liquid chromatography-mass spectrometry (LC-MS) device 10 also includes a third switching device and a fourth switching device. Multiple second chromatographic columns are connected in parallel between the third switching device and the fourth switching device. The second drive pump can be switched to multiple second chromatographic columns through the third switching device. The mass spectrometry detection device 200 can be switched to multiple second chromatographic columns through the fourth switching device.
[0059] In one implementation, the controller is also configured to control the first liquid chromatography channel 101 to drive the liquid fluid to perform gradient elution of the sample solution adsorbed on the first chromatographic column 110 to form a first analyte. In this implementation, the gradient elution scheme facilitates rapid separation and elution of the sample solution, thereby improving sample detection efficiency. The applicant's research has found that using a rapid gradient separation elution method, within a certain range, with a shorter first chromatographic column 110, provides better clinical detection performance.
[0060] In one implementation, the controller is further configured to: control the first liquid chromatography channel 101 to prepare liquid phase fluids of different concentrations from at least two liquids according to a first preset concentration control method, and drive the liquid phase fluids of different concentrations to perform gradient elution on the first test solution at a first working pressure, thereby forming the first analyte. The at least two liquids here include, for example, the first liquid and the second liquid described above. This embodiment prepares liquid phase fluids of different concentrations online using at least two liquids to meet the requirements for different concentrations of liquid phase fluids in gradient elution. Since the gradient elution uses the same set of eluents, the only difference being the mixing ratio control method of the first liquid and the second liquid, the amount of material and material costs can be effectively reduced.
[0061] In one embodiment, the first liquid chromatography channel 101 further includes a first confluence component 123, and two first drive pumps 121 are respectively connected to the first confluence component 123. One first drive pump 121 is used to draw a first liquid from the first container 20 and deliver the drawn first liquid toward the first confluence component 123 and the first chromatographic column 110. The other first drive pump 121 is used to draw a second liquid from the second container 30 and deliver the drawn second liquid toward the first confluence component 123 and the first chromatographic column 110. Before processing the mass spectrometry detection information, the controller is also configured to: control the two first drive pumps 121 to operate according to a first preset concentration control mode, so that the first liquid and / or the second liquid are made into liquid phase fluids of different concentrations in the first confluence component 123, and control the first drive pumps 121 to drive the liquid phase fluids of different concentrations in the first confluence component 123 to be delivered toward the chromatographic column respectively, so as to perform gradient elution of the test solution adsorbed on the chromatographic column to form the test solution.
[0062] In one implementation, the controller is also configured to control the second liquid chromatography channel 102 to drive the liquid fluid to perform gradient elution of the test solution adsorbed on the second chromatographic column to form a second test solution.
[0063] In one implementation, the controller is also configured to: control the second liquid chromatography channel 102 to prepare at least two liquids into liquid phase fluids of different concentrations according to a second preset concentration control method, and drive the liquid phase fluids of different concentrations to perform gradient elution on the second test solution with a second working pressure, thereby forming the second test solution.
[0064] As one implementation method, the pretreatment device 300 pretreatments the first and second samples using at least one of magnetic separation, solid-phase extraction, liquid-liquid extraction, and protein precipitation. Magnetic separation involves purifying the sample by adsorbing the target analyte with magnetic beads followed by elution, or by adsorbing impurities with magnetic beads. Solid-phase extraction (including magnetic solid-phase extraction) works by adjusting the solvent composition to control the adsorption and dissolution of the target analyte, thus extracting and enriching it. Liquid-liquid extraction (including solid-liquid extraction: solid-phase supported liquid-liquid extraction) separates and extracts the target analyte by utilizing the different partition coefficients of different substances in immiscible liquids. For example, 25-hydroxyvitamin D has a much higher partition coefficient in hexane than in water, and since hexane is immiscible with water, it can be extracted and separated using hexane. The principle of protein precipitation is as follows: proteins in serum / plasma are precipitated or separated by organic solvents, acids or metal salts, and then separated from the target analytes in the solution by centrifugation or filtration, thereby removing the protein background and extracting the target analytes.
[0065] In a first embodiment of the pretreatment device 300 employing magnetic separation, the pretreatment device 300 pretreatments samples using magnetic separation. The pretreatment device 300 includes a magnetic separation component 310, a magnetic bead elution component 320, a reagent dispensing component 340, and a pipetting component 350. The pipetting component 350 is used to aspirate at least a portion of the sample from the sample container of the sample storage device 400 and dispense all or part of the aspirated sample into the reaction container. The reagent dispensing component 340 is used to dispense the internal standard reagent and the first magnetic bead reagent into the reaction container, respectively. The magnetic separation component 310 is used to perform magnetic separation and washing on a first mixture containing at least the sample, the internal standard reagent, and the first magnetic bead reagent in the reaction container to obtain a first clear liquid and a first magnetic bead liquid, and to aspirate and drain the first clear liquid from the reaction container. The magnetic bead elution component 320 is used to elute the first magnetic bead liquid in the reaction container to obtain a test solution. The reagent transfer assembly 140 is used to aspirate at least a portion of the reagent from the reaction vessel and transfer all or part of the aspirated reagent to the reagent preparation channel. The reagent dispensing assembly 340 and the pipetting assembly 350 are either two independent components or the same component. In this embodiment, magnetic beads are used to adsorb the target analyte, which is in a first magnetic bead solution.
[0066] In one embodiment, the pretreatment device 300 further includes a reagent storage component 330 and a reagent dispensing component 340 for drawing at least a portion of the first magnetic bead reagent from the first reagent container of the reagent storage component 330 and dispensing all or part of the drawn first magnetic bead reagent to the reaction container.
[0067] In one embodiment, the pretreatment device 300 further includes a reaction vessel providing component 360 and a reaction vessel transferring component. The reaction vessel providing component 360 is used to provide a reaction vessel, and the reaction vessel transferring component is used to transfer the reaction vessel from the reaction vessel providing component 360 to the magnetic separation component 310 and the magnetic bead elution component 320, respectively.
[0068] In one embodiment, the pretreatment device 300 further includes a mixing component; the controller is also configured to control the pretreatment device 300 to perform the following pretreatment actions: control the pipetting component 350 to aspirate at least a portion of the sample from the sample container of the sample storage device 400 and distribute all or part of the aspirated sample to the reaction container; control the reagent dispensing component 340 to dispense the internal standard reagent to the reaction container; control the mixing component to mix the sample and the internal standard reagent in the reaction container to obtain a second mixture; control the reagent dispensing component 340 to dispense the first magnetic bead reagent into the second mixture in the reaction container to obtain a first mixture; control the magnetic separation component 310 to perform magnetic separation and washing on the first mixture in the reaction container to obtain a first clear liquid and a first magnetic bead liquid; control the magnetic separation component 310 to aspirate and drain the first clear liquid from the reaction container; control the magnetic bead elution component 320 to elute the first magnetic bead liquid in the reaction container to obtain a test solution. In a second embodiment of the pretreatment device 300 employing magnetic separation, the pretreatment device 300 pretreatments samples using magnetic separation. The pretreatment device 300 includes a magnetic separation component 310, a reagent dispensing component 340, and a pipetting component 350. The pipetting component 350 aspirates at least a portion of the sample from the sample container of the sample storage device 400 and dispenses all or part of the aspirated sample into the reaction container. The reagent dispensing component 340 dispenses the internal standard reagent and the second magnetic bead reagent into the reaction container, respectively. The magnetic separation component 310 performs magnetic separation and cleaning on the third mixture in the reaction container, which contains at least the sample, the internal standard reagent, and the second magnetic bead reagent, to obtain a second clear liquid and a second magnetic bead liquid. The second clear liquid is used as the test solution. The test solution transfer component 140 aspirates at least a portion of the test solution from the reaction container and transfers all or part of the aspirated test solution to the test solution preparation channel. The reagent dispensing component 340 and the pipetting component 350 are either two independent components or the same component. In this embodiment, the magnetic beads are used to adsorb impurities, and the target analyte is in the second clear liquid.
[0069] In one embodiment, the liquid chromatography-mass spectrometry (LC-MS) apparatus 10 further includes an information acquisition device for acquiring at least one of the following: information about a sample container, and information about a sample loaded in the sample container; wherein the sample information includes at least sample type information and / or analyte information of the sample. The controller is further configured to: determine, based on information fed back from the information acquisition device, the type of a sample container placed in or from a sample storage device, or the type of a sample loaded in a sample container placed in or from a sample storage device, or the analyte information of a sample placed in or from a sample container in a sample storage device 400; when the information fed back from the information acquisition device determines that the type of the sample container placed in or from the sample storage device 400 is a first sample container, or determines that the type of the sample in the sample container placed in or from the sample storage device 400 is a first sample, or determines that the type of the sample ... The sample container of the sample storage device 400 contains a first target item as the analyte. The pretreatment device 300 pretreatments the sample in the sample container to obtain a first test solution. The test solution transfer component 140 transfers at least a portion of the first test solution obtained by the pretreatment device 300 to the first liquid chromatography channel 101. The first liquid chromatography channel 101 is controlled to drive the liquid phase fluid at a first working pressure to elute the first test solution to form a first analyte. The mass spectrometry detection device 200 performs mass spectrometry detection on the first analyte flowing out of the first liquid chromatography channel 101 and obtains the first mass spectrometry detection information. When the information obtained from the information acquisition device determines that the sample container placed in or from the sample storage device 400 is a second sample container, or that the sample placed in or from the sample storage device 400 is a second sample, or that the analyte in the sample placed in or from the sample storage device 400 contains a second target item, the pretreatment device 300 is controlled to pretreatment the sample in the sample container to obtain a second test solution. The test solution transfer assembly 140 is controlled to transfer at least a portion of the second test solution obtained by the pretreatment device 300 to the second liquid chromatography channel 102. The second liquid chromatography channel 102 is controlled to drive the liquid phase fluid at a second working pressure to elute the second test solution to form a second analyte. The mass spectrometry detection device 200 is controlled to perform mass spectrometry detection on the second analyte flowing out of the second liquid chromatography channel 102 and obtain second mass spectrometry detection information. In this embodiment, information about the sample and / or sample container is obtained through information identification, thereby controlling the transfer of the sample to the first liquid chromatography channel 101 or the second liquid chromatography channel 102 for elution.
[0070] In one implementation, the information acquisition device includes at least one of the following devices: a scanning device for scanning an identification code on a sample container, and a camera device for capturing an image of the sample container. The identification code includes at least one of a QR code, a barcode, and a radio frequency code.
[0071] In one implementation, the sample storage device 400 is provided with a first loading area and a second loading area independent of the first loading area. The first loading area is used to place a first sample container containing a first sample to achieve loading of the first sample, and the second loading area is used to place a second sample container containing a second sample to achieve loading of the second sample. Before processing the first mass spectrometry detection information, the controller is further configured to: acquire information that a sample container is placed in the first loading area; control the pretreatment device 300 to pretreat the sample in the sample container to obtain a first test solution; control the test solution transfer component 140 to transfer at least a portion of the first test solution obtained by the pretreatment device 300 to the first liquid chromatography channel 101; control the first liquid chromatography channel 101 to drive the liquid phase fluid at a first working pressure to elute the first test solution to form a first analyte; and control the mass spectrometry detection device 200 to perform mass spectrometry detection on the first analyte flowing out of the first liquid chromatography channel 101 and obtain the first mass spectrometry detection information. Before processing the second mass spectrometry detection information, the controller is further configured to: acquire information that a sample container is placed in the second loading area; control the pretreatment device 300 to pretreatment the sample in the sample container to obtain a second test solution; control the test solution transfer assembly 140 to transfer at least a portion of the second test solution obtained by the pretreatment device 300 to the second liquid chromatography channel 102; control the second liquid chromatography channel 102 to drive the liquid phase fluid at a second working pressure to elute the second test solution to form a second analyte; and control the mass spectrometry detection device 200 to perform mass spectrometry detection on the second analyte flowing out of the second liquid chromatography channel 102 and obtain the second mass spectrometry detection information. In this embodiment, through sample partitioning loading, the sample is controlled to be transferred to the first liquid chromatography channel 101 or the second liquid chromatography channel 102 for elution.
[0072] In one implementation, the mass spectrometry detection device 200 includes a triple quadrupole tandem mass spectrometer.
[0073] In one implementation, the first liquid chromatography channel 101 or the second liquid chromatography channel 102 may share the same column temperature device or use different column temperature devices separately.
[0074] The embodiments of the present invention can simultaneously and flexibly switch between the low-pressure liquid chromatography channel (first liquid chromatography channel 101) and the high-pressure liquid chromatography channel (second liquid chromatography channel 102) to perform routine clinical mass spectrometry detection, including the detection of vitamin D, steroid hormones, catecholamines and drug concentrations.
[0075] As one implementation method, the length of the chromatographic column is greater than or equal to 3 mm and less than or equal to 35 mm.
[0076] In one implementation, the length of the chromatographic column is 25 mm, 3 mm, 30 mm, 20 mm, 10 mm, or 15 mm.
[0077] In one implementation, the working pressure output by the liquid phase fluid transport component is 10 MPa, 15 MPa, or 20 MPa.
[0078] In one embodiment, the pretreatment device further includes a reagent storage component for loading a first reagent container containing an internal standard reagent and a second reagent container containing magnetic bead reagents. The reagent dispensing component is used to draw at least a portion of the internal standard reagent from the first reagent container of the reagent storage component and dispense all or part of the drawn internal standard reagents into the reaction vessel, and to draw at least a portion of the magnetic bead reagents from the second reagent container of the reagent storage component and dispense all or part of the drawn magnetic bead reagents into the reaction vessel.
[0079] In one implementation, the preprocessing device further includes a mixing component; the controller is also configured to control the preprocessing device to perform the following preprocessing actions: Control the pipetting component to aspirate at least a portion of the sample from the sample container of the sample storage device and to dispense all or part of the aspirated sample into the reaction container; The reagent dispensing unit controls the dispensing of internal standard reagents into the reaction vessel; The mixing unit is controlled to mix the sample and internal standard reagent in the reaction vessel to obtain a second mixture; The reagent dispensing component controls the magnetic bead reagent to be dispensed into the second mixture in the reaction vessel to obtain the first mixture. The magnetic separation component is controlled to perform magnetic separation and cleaning of the first mixture in the reaction vessel to obtain a clear liquid and magnetic beads adsorbed with internal standard and target analyte; The magnetic separation component is controlled to draw in and drain the clear liquid from the reaction vessel; The magnetic bead elution unit controls the elution of magnetic beads containing internal standards and target analytes in the reaction vessel to obtain the test solution.
[0080] Compared with previous technical solutions, the key innovations in the technical performance of the liquid chromatography-mass spectrometry (LC-MS) device 10 provided in this application are as follows: 1) Previous chromatographic techniques used longer columns (e.g., 50 mm) to increase the theoretical plate number of the separation. However, this theoretical plate number is suitable for long-duration separations requiring partial isocratic elution, such as the analysis of complex research samples, or for increasing the flow rate to appropriately shorten the analysis time, but this results in extremely high system pressure. In contrast, this application addresses the need for rapid and efficient clinical testing. From another perspective, it employs a rapid gradient separation elution method. Within a certain range, using a shorter column (e.g., 5 mm-30 mm) provides better clinical testing performance. Furthermore, it only requires a low flow rate (e.g., 0.3 mL / min-0.6 mL / min) to quickly complete the analysis, resulting in better peak widths of the separated analytes. Simultaneously, the shorter column (110) leads to lower system pressure, demonstrating significant advantages. See [link to specific effects] for details. Figure 4 As shown.
[0081] 2) Previous chromatographic techniques used columns with smaller inner diameters to minimize lateral diffusion during separation and reduce column bed volume, thus shortening dead time. However, excessively small inner diameters lead to a significant increase in column pressure, increasing system pressure, and also increase the longitudinal width of the target analyte binding with the column material, resulting in broader peaks and affecting resolution. Therefore, this application employs a 2.1mm-4.0mm column with an inner diameter of 110, which differs from previous ultra-high efficiency UHPLC techniques (column inner diameter of 1.0mm-2.1mm) and conventional HPLC techniques (column inner diameter of 4.6mm-10mm). This achieves both low pressure and high resolution. For specific results, please refer to [link to relevant documentation]. Figure 5 As shown.
[0082] 3) This application's embodiments, targeting the sample types, analyte concentrations, and sensitivity requirements for clinical testing of vitamin D and steroid hormones, select and design key column (packing) parameters (particle size 1.7, 1.8 μm), balancing column pressure and specific surface area to achieve better analyte retention and resolution. For specific results, please refer to [link to relevant documentation]. Figure 6 As shown.
[0083] 4) Balanced control of overall column bed volume: If the column bed volume is too large, the retention of the target analyte will be too strong, which is not conducive to rapid elution and separation. At the same time, it will increase the loss of the target analyte due to non-specific adsorption, resulting in a decrease in recovery rate and sensitivity. If the column bed volume is too small, the retention of the target analyte will be too weak or supersaturation will occur, resulting in sample loss and affecting retention separation and sensitivity. The embodiments of this application optimize the design of column bed volume (0.063mL-0.38mL) suitable for rapid separation in clinical detection of vitamin D and steroid hormones.
[0084] 5) The specific optimization parameters and beneficial effects are shown in Table 1 below: Table 1
[0085] To verify the beneficial effects of the liquid chromatography-mass spectrometry (LC-MS) device 10 provided in the embodiments of this application, the applicant conducted the following experiments: (1) Example 1 Samples from the same sample container were divided into two portions. One portion was used for steroid hormone detection using a first liquid chromatography-mass spectrometry (LC-MS) device (i.e., the LC-MS device 10 provided in this application embodiment) employing a chromatographic column 110 with an inner diameter of 3.0 mm and a length of 25 mm and a working column pressure of 10 MPa. The other portion was used for steroid hormone detection using a second LC-MS device (i.e., the LC-MS device provided in the prior art of this application) employing a chromatographic column with an inner diameter of 2.1 mm and a length of 50 mm and a working column pressure of 40 MPa. The results were as follows: Figure 7 And the detection data in Table 2 below.
[0086] Table 2
[0087] according to Figure 7 As shown in Table 2, for the LC-MS detection of steroid hormones, the low-pressure chromatography separation technique of this application embodiment, besides significantly reducing the working column pressure from 40 MPa to 10 MPa, also exhibits superior performance compared to the high-pressure chromatography separation of previous related techniques, such as significantly reduced peak width, increased peak height, and slightly improved resolution. Furthermore, the low-pressure chromatography separation technique of this application embodiment can achieve an earlier first peak elution time, resulting in higher separation and detection efficiency.
[0088] Example 2: Samples from the same sample container were divided into two portions. One portion was used for vitamin D detection using a first liquid chromatography-mass spectrometry (LC-MS) device (i.e., the LC-MS device 10 provided in this embodiment) with a chromatographic column of 3.0 mm inner diameter and 25 mm length and a working column pressure of 10 MPa. The other portion was used for vitamin D detection using a second LC-MS device (i.e., the LC-MS device provided in the prior art) with a chromatographic column of 2.1 mm inner diameter and 50 mm length and a working column pressure of 40 MPa. The results were as follows: Figure 8 And the detection data in Table 3 below.
[0089] Table 3
[0090] according to Figure 8 As shown in Table 3, for the LC-MS detection of vitamin D, the low-pressure chromatography separation technology of this application embodiment, except for a significant reduction in working column pressure from 40 MPa to 10 MPa, maintains or even outperforms the high-pressure chromatography separation performance of previous related technologies, such as peak width, peak height, and resolution. Furthermore, the low-pressure chromatography separation technology of this application embodiment can achieve an earlier first peak elution time, resulting in higher separation and detection efficiency.
[0091] A second aspect of the present invention provides a liquid chromatography-mass spectrometry (LC-MS) device 10, the LC-MS device 10 comprising: The sample storage device 400 is used to place a first sample container loaded with a first sample to realize the feeding of the first sample, and to place a second sample container loaded with a second sample to realize the feeding of the second sample. The pretreatment device 300 is used to pretreatment a first sample from a first sample container of a sample storage device 400 to obtain a first test solution, and to pretreatment a second sample from a second sample container of a sample storage device 400 to obtain a second test solution. The chromatographic device 100 includes a reagent transfer assembly 140, at least one first liquid chromatography channel 101, and at least one second liquid chromatography channel 102. The reagent transfer assembly 140 is used to transfer at least a portion of the first reagent obtained by the pretreatment device 300 to the first liquid chromatography channel 101 and to transfer at least a portion of the second reagent obtained by the pretreatment device 300 to the second liquid chromatography channel 102. The first liquid chromatography channel 101 is used to drive a liquid fluid to elute the first reagent to form a first analyte, and the second liquid chromatography channel 102 is used to drive a liquid fluid to elute the second reagent to form a second analyte. The mass spectrometry detection device 200 has at least one first liquid chromatography channel 101 and at least one second liquid chromatography channel 102 respectively connected to the same mass spectrometry detection device 200. The mass spectrometry detection device 200 is used to perform mass spectrometry detection on the first test liquid flowing out of the first liquid chromatography channel 101 and obtain first mass spectrometry detection information, and to perform mass spectrometry detection on the second test liquid flowing out of the second liquid chromatography channel 102 and obtain second mass spectrometry detection information. The controller is configured to process the first mass spectrometry detection information and output the mass spectrometry detection result of the first sample. The controller is also configured to process the second mass spectrometry detection information and output the mass spectrometry detection results of the second sample; The first sample and the second sample are two different samples; The first sample container and the second sample container are two independent sample containers; The first liquid chromatography channel 101 includes at least one first chromatographic column 110, and the second liquid chromatography channel 102 includes at least one second chromatographic column, wherein the size parameters of the first chromatographic column 110 are different from the size parameters of the second chromatographic column.
[0092] In one embodiment, the first chromatographic column 110 includes a first column having a first inner cavity 111 and a first packing material filled in the first inner cavity 111; the second chromatographic column includes a second column having a second inner cavity and a second packing material filled in the second inner cavity; the dimensional parameters of the first chromatographic column 110 are different from the dimensional parameters of the second chromatographic column, including at least one of the following situations: the length L of the first chromatographic column is less than the length of the second chromatographic column, and the inner diameter dd of the first inner cavity 111 is greater than the inner diameter dd of the second inner cavity.
[0093] In one implementation, the length L of the first chromatographic column is greater than or equal to 5 mm and less than or equal to 30 mm, and the length of the second chromatographic column is greater than or equal to 50 mm and less than or equal to 150 mm.
[0094] In one embodiment, the inner diameter dd of the first inner cavity 111 is greater than 2.1 mm and less than or equal to 4.0 mm, and the inner diameter dd of the second inner cavity is greater than or equal to 1.0 mm and less than or equal to 2.1 mm.
[0095] Apart from the above, other parts and principles of the liquid chromatography-mass spectrometry (LC-MS) device 10 provided in the second aspect of the present invention can be referred to the liquid chromatography-mass spectrometry (LC-MS) device 10 provided in the first aspect above, and will not be described in detail here.
[0096] A third aspect of the present invention provides a liquid chromatography-mass spectrometry (LC-MS) device 10, the LC-MS device 10 comprising: The sample storage device 400 is used to place a first sample container loaded with a first sample to realize the feeding of the first sample, and to place a second sample container loaded with a second sample to realize the feeding of the second sample. The pretreatment device 300 is used to pretreatment a first sample from a first sample container of a sample storage device 400 to obtain a first test solution, and to pretreatment a second sample from a second sample container of a sample storage device 400 to obtain a second test solution. The chromatographic device 100 includes a reagent transfer assembly 140, at least one first liquid chromatography channel 101, and at least one second liquid chromatography channel 102. The reagent transfer assembly 140 is used to transfer at least a portion of the first reagent obtained by the pretreatment device 300 to the first liquid chromatography channel 101 and to transfer at least a portion of the second reagent obtained by the pretreatment device 300 to the second liquid chromatography channel 102. The first liquid chromatography channel 101 is used to drive a liquid fluid to elute the first reagent to form a first analyte, and the second liquid chromatography channel 102 is used to drive a liquid fluid to elute the second reagent to form a second analyte. The mass spectrometry detection device 200 has at least one first liquid chromatography channel 101 and at least one second liquid chromatography channel 102 respectively connected to the same mass spectrometry detection device 200. The mass spectrometry detection device 200 is used to perform mass spectrometry detection on the first test liquid flowing out of the first liquid chromatography channel 101 and obtain first mass spectrometry detection information, and to perform mass spectrometry detection on the second test liquid flowing out of the second liquid chromatography channel 102 and obtain second mass spectrometry detection information. The controller is configured to process the first mass spectrometry detection information and output the mass spectrometry detection result of the first sample. The controller is also configured to process the second mass spectrometry detection information and output the mass spectrometry detection results of the second sample; The first sample and the second sample are two different samples; The first sample container and the second sample container are two independent sample containers; The first liquid chromatography channel 101 includes at least one first drive pump 121, and the second liquid chromatography channel 102 includes at least one second drive pump. The rated operating pressure of the first drive pump 121 is less than or equal to 20 MPa, and the rated operating pressure of the second drive pump is greater than 20 MPa.
[0097] In one embodiment, the rated operating pressure of the first drive pump 121 is greater than or equal to 2 MPa and less than or equal to 15 MPa, and the rated operating pressure of the second drive pump is greater than or equal to 40 MPa; or, the rated operating pressure of the first drive pump 121 is greater than or equal to 2 MPa and less than or equal to 15 MPa, and the rated operating pressure of the first drive pump 121 is greater than or equal to 60 MPa; or, the rated operating pressure of the first drive pump 121 is greater than or equal to 2 MPa and less than or equal to 15 MPa, and the rated operating pressure of the first drive pump 121 is greater than or equal to 80 MPa.
[0098] Apart from the above, other parts and principles of the liquid chromatography-mass spectrometry (LC-MS) device 10 provided in the third aspect of the present invention can be referred to the LC-MS device 10 provided in the first and second aspects above, and will not be described in detail here.
[0099] The above description is merely a preferred embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent structural transformations made using the contents of the present invention's specification and drawings under the inventive concept of the present invention, or direct / indirect applications in other related technical fields, are included within the patent protection scope of the present invention.
Claims
1. A liquid chromatography-mass spectrometry (LC-MS) device, characterized in that: include: A sample storage device, the sample storage device being used to place a first sample container loaded with a first sample to realize the loading of the first sample, and to place a second sample container loaded with a second sample to realize the loading of the second sample, the first sample including a target analyte; A pretreatment device for pretreating a first sample from a first sample container of the sample storage device to obtain a first test solution, and for pretreating a second sample from a second sample container of the sample storage device to obtain a second test solution. A chromatographic device, comprising a reagent transfer assembly, at least one first liquid chromatography channel, and at least one second liquid chromatography channel, wherein the reagent transfer assembly is used to transfer at least a portion of the first reagent obtained by pretreatment by the pretreatment device to the first liquid chromatography channel and to transfer at least a portion of the second reagent obtained by pretreatment by the pretreatment device to the second liquid chromatography channel, wherein the first liquid chromatography channel is used to drive a liquid fluid at a first working pressure to elute the first reagent to form a first analyte, and the second liquid chromatography channel is used to drive a liquid fluid at a second working pressure to elute the second reagent to form a second analyte; A mass spectrometry detection device, wherein at least one first liquid chromatography channel and at least one second liquid chromatography channel are respectively connected to the same mass spectrometry detection device, the mass spectrometry detection device is used to perform mass spectrometry detection on the first test liquid flowing out of the first liquid chromatography channel and obtain first mass spectrometry detection information, and is used to perform mass spectrometry detection on the second test liquid flowing out of the second liquid chromatography channel and obtain second mass spectrometry detection information. A controller configured to process the first mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the first sample; The controller is also configured to process the second mass spectrometry detection information and output the mass spectrometry detection result of the second sample; The first sample and the second sample are two different samples; The first sample container and the second sample container are two independent sample containers; The first working pressure is less than or equal to 20 MPa, and the second working pressure is greater than 20 MPa.
2. The liquid chromatography-mass spectrometry (LC-MS) device as described in claim 1, characterized in that: The second working pressure is greater than or equal to 40 MPa.
3. The liquid chromatography-mass spectrometry (LC-MS) device as described in claim 2, characterized in that: The second working pressure is greater than or equal to 60 MPa.
4. The liquid chromatography-mass spectrometry (LC-MS) device as described in claim 3, characterized in that: The second working pressure is greater than or equal to 80 MPa.
5. The liquid chromatography-mass spectrometry (LC-MS) apparatus according to any one of claims 1 to 4, characterized in that: The first working pressure is greater than or equal to 2 MPa and less than or equal to 15 MPa.
6. The liquid chromatography-mass spectrometry (LC-MS) apparatus according to any one of claims 1 to 4, characterized in that: The first liquid chromatography channel includes a first reagent preparation channel, at least one first drive pump, and at least one first chromatographic column. The reagent transfer assembly, the first drive pump, and the first chromatographic column are respectively connected to the first reagent preparation channel. The reagent transfer assembly is used to transfer at least a portion of the first reagent obtained by the pretreatment device to the first reagent preparation channel. The at least one first drive pump is used to drive the first reagent in the first reagent preparation channel through the chromatographic column to adsorb the first reagent onto the chromatographic column, and to drive the liquid fluid through the chromatographic column to elute the first reagent adsorbed on the chromatographic column to form the first test solution. The second liquid chromatography channel includes a second reagent preparation channel, at least one second drive pump, and at least one second chromatographic column. The reagent transfer assembly, the second drive pump, and the second chromatographic column are respectively connected to the second reagent preparation channel. The reagent transfer assembly is used to transfer at least a portion of the second reagent obtained by the pretreatment device to the second reagent preparation channel. The at least one second drive pump is used to drive the second reagent in the second reagent preparation channel through the chromatographic column to adsorb the second reagent onto the chromatographic column, and to drive the liquid fluid through the chromatographic column to elute the second reagent adsorbed on the chromatographic column to form the second test solution. The rated working pressure of the first drive pump is less than or equal to 20 MPa, and the rated working pressure of the second drive pump is greater than 20 MPa. The dimensional parameters of the first chromatographic column are different from those of the second chromatographic column; The first test solution preparation channel and the second test solution preparation channel may be the same test solution preparation channel or different test solution preparation channels.
7. The liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 6, characterized in that: The first chromatographic column includes a first column having a first inner cavity and a first packing material filled in the first inner cavity; The second chromatographic column includes a second column having a second inner cavity and a second packing material filled within the second inner cavity; The dimensional parameters of the first chromatographic column are different from those of the second chromatographic column, including at least one of the following situations: the length of the first chromatographic column is less than the length of the second chromatographic column, and the inner diameter of the first inner cavity is greater than the inner diameter of the second inner cavity.
8. The liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 7, characterized in that: The length of the first chromatographic column is greater than or equal to 5 mm and less than or equal to 30 mm, and the length of the second chromatographic column is greater than or equal to 50 mm and less than or equal to 150 mm. And / or, the inner diameter of the first inner cavity is greater than 2.1 mm and less than or equal to 4.0 mm, and the inner diameter of the second inner cavity is greater than or equal to 1.0 mm and less than or equal to 2.1 mm.
9. The liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 7, characterized in that: The volume of the first inner cavity is greater than or equal to 0.063 mL and less than or equal to 0.38 mL.
10. The liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 6, characterized in that: The second drive pump is also configured to switchly connect to at least one of the first chromatographic columns; The second drive pump has a first working mode and a second working mode. In the first working mode, the second drive pump is used to communicate with the second chromatographic column and drive the liquid phase fluid at the second working pressure to elute the second test solution adsorbed on the second chromatographic column to form the second test solution. In the second working mode, the second drive pump is used to communicate with the first chromatographic column and drive the liquid phase fluid at the first working pressure to elute the first test solution adsorbed on the first chromatographic column to form the first test solution.
11. The liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 6, characterized in that: The number of the first chromatographic columns is multiple. The liquid chromatography-mass spectrometry (LC-MS) device also includes a first switching device and a second switching device. The multiple first chromatographic columns are connected in parallel between the first switching device and the second switching device. The first drive pump can switch to connect to the multiple first chromatographic columns through the first switching device. The mass spectrometry detection device can switch to connect to the multiple first chromatographic columns through the second switching device. And / or, the number of the second chromatographic columns is multiple, and the liquid chromatography-mass spectrometry device further includes a third switching device and a fourth switching device. The multiple second chromatographic columns are connected in parallel between the third switching device and the fourth switching device. The second drive pump can switch to connect to the multiple second chromatographic columns through the third switching device, and the mass spectrometry detection device can switch to connect to the multiple second chromatographic columns through the fourth switching device.
12. The liquid chromatography-mass spectrometry apparatus according to any one of claims 1 to 4, characterized in that: The target analyte includes at least one of vitamin D, steroid hormones, and catecholamines; And / or, the output of the mass spectrometry detection results of the first sample includes: outputting the mass spectrometry detection results of at least one of vitamin D, steroid hormones, and catecholamines in the first sample.
13. The liquid chromatography-mass spectrometry apparatus according to any one of claims 1 to 4, characterized in that: Both the first sample and the second sample were collected from human or animal samples; And / or, both the first sample and the second sample are blood samples.
14. The liquid chromatography-mass spectrometry apparatus according to any one of claims 1 to 4, characterized in that: The controller is further configured to: control the first liquid chromatography channel to prepare at least two liquids into liquid phase fluids of different concentrations according to a first preset concentration control method, and drive the liquid phase fluids of different concentrations to perform gradient elution on the first test solution at the first working pressure, thereby forming the first test solution; And / or, the controller is further configured to: control the second liquid chromatography channel to prepare at least two liquids into liquid phase fluids of different concentrations according to a second preset concentration control method, and drive the liquid phase fluids of different concentrations to perform gradient elution on the second test solution with the second working pressure, thereby forming the second test solution.
15. The liquid chromatography-mass spectrometry apparatus according to any one of claims 1 to 4, characterized in that: The pretreatment device uses at least one of magnetic separation, solid-phase extraction, liquid-liquid extraction, and protein precipitation to pretreatment the first sample and the second sample, respectively.
16. The liquid chromatography-mass spectrometry apparatus according to any one of claims 1 to 4, characterized in that: The liquid chromatography-mass spectrometry (LC-MS) device further includes an information acquisition device, which is used to acquire at least one of the following information: information about the sample container, and information about the sample loaded in the sample container; wherein the information about the sample includes at least the type information of the sample and / or the analyte information of the sample; Before processing the first mass spectrometry detection information or the second mass spectrometry detection information, the controller is further configured to: Based on the information obtained from the device feedback, determine the type of the sample container from the sample storage device, or determine the type of sample loaded in the sample container from the sample storage device, or determine the test item information of the sample in the sample container from the sample storage device. When the information obtained from the information acquisition device feedback determines that the sample container from the sample storage device is of the first sample container type, or determines that the sample from the sample container from the sample storage device is of the first sample type, or determines that the test item of the sample from the sample container from the sample storage device contains the first target item, the pretreatment device is controlled to pretreatment the sample in the sample container to obtain the first test solution, the test solution transfer component is controlled to transfer at least a portion of the first test solution obtained by the pretreatment device to the first liquid chromatography channel, the first liquid chromatography channel is controlled to drive the liquid phase fluid at the first working pressure to elute the first test solution to form the first test solution, and the mass spectrometry detection device is controlled to perform mass spectrometry detection on the first test solution flowing out of the first liquid chromatography channel and obtain the first mass spectrometry detection information. When the information obtained from the information acquisition device feedback determines that the sample container from the sample storage device is the second sample container, or determines that the sample in the sample container from the sample storage device is the second sample, or determines that the test item of the sample in the sample container from the sample storage device contains the second target item, the pretreatment device is controlled to pretreatment the sample in the sample container to obtain the second test solution, the test solution transfer component is controlled to transfer at least a portion of the second test solution obtained by the pretreatment device to the second liquid chromatography channel, the second liquid chromatography channel is controlled to drive the liquid phase fluid to elute the second test solution at the second working pressure to form the second test solution, and the mass spectrometry detection device is controlled to perform mass spectrometry detection on the second test solution flowing out of the second liquid chromatography channel and obtain the second mass spectrometry detection information; Alternatively, the sample storage device may have a first loading area and a second loading area independent of the first loading area. The first loading area is used to place the first sample container containing the first sample to load the first sample, and the second loading area is used to place the second sample container containing the second sample to load the second sample. Before processing the first mass spectrometry detection information, the controller is further configured to: acquire information that a sample container is placed in the first loading area; control the pretreatment device to pretreat the sample in the sample container to obtain the first test solution; control the test solution transfer component to transfer at least a portion of the first test solution obtained by the pretreatment device to the first liquid chromatography channel; control the first liquid chromatography channel to drive the liquid phase fluid at the first working pressure to elute the first test solution to form the first test solution; and control the mass spectrometry detection device to perform mass spectrometry detection on the first test solution flowing out of the first liquid chromatography channel and obtain the first mass spectrometry detection information. Before processing the second mass spectrometry detection information, the controller is further configured to: acquire information that a sample container is placed in the second loading area; control the pretreatment device to pretreat the sample in the sample container to obtain the second test solution; control the test solution transfer component to transfer at least a portion of the second test solution obtained by the pretreatment device to the second liquid chromatography channel; control the second liquid chromatography channel to drive the liquid phase fluid at the second working pressure to elute the second test solution to form the second test solution; and control the mass spectrometry detection device to perform mass spectrometry detection on the second test solution flowing out of the second liquid chromatography channel and obtain the second mass spectrometry detection information.
17. A liquid chromatography-mass spectrometry (LC-MS) device, characterized in that: include: A sample storage device, the sample storage device being used to place a first sample container loaded with a first sample to realize the loading of the first sample, and to place a second sample container loaded with a second sample to realize the loading of the second sample, the first sample including a target analyte; A pretreatment device for pretreating a first sample from a first sample container of the sample storage device to obtain a first test solution, and for pretreating a second sample from a second sample container of the sample storage device to obtain a second test solution. A chromatographic device, comprising a reagent transfer assembly, at least one first liquid chromatography channel, and at least one second liquid chromatography channel, wherein the reagent transfer assembly is used to transfer at least a portion of the first reagent obtained by pretreatment by the pretreatment device to the first liquid chromatography channel and to transfer at least a portion of the second reagent obtained by pretreatment by the pretreatment device to the second liquid chromatography channel, wherein the first liquid chromatography channel is used to drive a liquid fluid to elute the first reagent to form a first analyte, and the second liquid chromatography channel is used to drive a liquid fluid to elute the second reagent to form a second analyte; A mass spectrometry detection device, wherein at least one first liquid chromatography channel and at least one second liquid chromatography channel are respectively connected to the same mass spectrometry detection device, the mass spectrometry detection device is used to perform mass spectrometry detection on the first test liquid flowing out of the first liquid chromatography channel and obtain first mass spectrometry detection information, and is used to perform mass spectrometry detection on the second test liquid flowing out of the second liquid chromatography channel and obtain second mass spectrometry detection information. A controller configured to process the first mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the first sample; The controller is also configured to process the second mass spectrometry detection information and output the mass spectrometry detection result of the second sample; The first sample and the second sample are two different samples; The first sample container and the second sample container are two independent sample containers; The first liquid chromatography channel includes at least one first chromatographic column, and the second liquid chromatography channel includes at least one second chromatographic column, wherein the size parameters of the first chromatographic column are different from the size parameters of the second chromatographic column.
18. The liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 17, characterized in that: The first chromatographic column includes a first column having a first inner cavity and a first packing material filled in the first inner cavity; The second chromatographic column includes a second column having a second inner cavity and a second packing material filled within the second inner cavity; The dimensional parameters of the first chromatographic column are different from those of the second chromatographic column, including at least one of the following situations: the length of the first chromatographic column is less than the length of the second chromatographic column, and the inner diameter of the first inner cavity is greater than the inner diameter of the second inner cavity.
19. The liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 18, characterized in that: The length of the first chromatographic column is greater than or equal to 5 mm and less than or equal to 30 mm, and the length of the second chromatographic column is greater than or equal to 50 mm and less than or equal to 150 mm. And / or, the inner diameter of the first inner cavity is greater than 2.1 mm and less than or equal to 4.0 mm, and the inner diameter of the second inner cavity is greater than or equal to 1.0 mm and less than or equal to 2.1 mm.
20. A liquid chromatography-mass spectrometry (LC-MS) device, characterized in that: include: A sample storage device, the sample storage device being used to place a first sample container loaded with a first sample to realize the loading of the first sample, and to place a second sample container loaded with a second sample to realize the loading of the second sample, the first sample including a target analyte; A pretreatment device for pretreating a first sample from a first sample container of the sample storage device to obtain a first test solution, and for pretreating a second sample from a second sample container of the sample storage device to obtain a second test solution. A chromatographic device, comprising a reagent transfer assembly, at least one first liquid chromatography channel, and at least one second liquid chromatography channel, wherein the reagent transfer assembly is used to transfer at least a portion of the first reagent obtained by pretreatment by the pretreatment device to the first liquid chromatography channel and to transfer at least a portion of the second reagent obtained by pretreatment by the pretreatment device to the second liquid chromatography channel, wherein the first liquid chromatography channel is used to drive a liquid fluid to elute the first reagent to form a first analyte, and the second liquid chromatography channel is used to drive a liquid fluid to elute the second reagent to form a second analyte; A mass spectrometry detection device, wherein at least one first liquid chromatography channel and at least one second liquid chromatography channel are respectively connected to the same mass spectrometry detection device, the mass spectrometry detection device is used to perform mass spectrometry detection on the first test liquid flowing out of the first liquid chromatography channel and obtain first mass spectrometry detection information, and is used to perform mass spectrometry detection on the second test liquid flowing out of the second liquid chromatography channel and obtain second mass spectrometry detection information. A controller configured to process the first mass spectrometry detection information and output the mass spectrometry detection result of the target analyte in the first sample; The controller is also configured to process the second mass spectrometry detection information and output the mass spectrometry detection result of the second sample; The first sample and the second sample are two different samples; The first sample container and the second sample container are two independent sample containers; The first liquid chromatography channel includes at least one first drive pump, and the second liquid chromatography channel includes at least one second drive pump. The rated operating pressure of the first drive pump is less than or equal to 20 MPa, and the rated operating pressure of the second drive pump is greater than 20 MPa.
21. The liquid chromatography-mass spectrometry (LC-MS) apparatus as described in claim 20, characterized in that: The rated operating pressure of the first drive pump is greater than or equal to 2MPa and less than or equal to 15MPa, and the rated operating pressure of the second drive pump is greater than or equal to 40MPa. Alternatively, the rated operating pressure of the first drive pump is greater than or equal to 2 MPa and less than or equal to 15 MPa, or the rated operating pressure of the first drive pump is greater than or equal to 60 MPa. Alternatively, the rated operating pressure of the first drive pump is greater than or equal to 2 MPa and less than or equal to 15 MPa, or the rated operating pressure of the first drive pump is greater than or equal to 80 MPa.